Project Summary/Abstract Our long-range goal is to understand signal transduction pathways underlying energy homeostasis and how their alterations contribute to obesity and metabolic diseases. Brown fat and brown-like fat are specialized in energy expenditure. They are present in adult humans and their activity is inversely associated with human obesity. Thus, brown fat and brown-like fat represent potential therapeutic target for obesity and metabolic diseases. We are interested in discovering novel adipokines controlling `browning' of white fat. We identified a previously uncharacterized, secreted protein that is specifically expressed in brown fat and brown-like fat. Our preliminary data showed that this adipokine plays a key part in brown fat-selective gene expression and energy expenditure. We hypothesized that this adipokine, through paracrine and endocrine actions, controls thermogenic gene program, and is both necessary and sufficient for white fat browning. In the first aim, we will investigate in detail the roles of this adipokine in thermogenic gene expression in primary adipocyte culture and its underlying mechanism. In the second aim, we will perform gain-of-functional studies to analyze the metabolic phenotype of this adipokine in vivo. In the third aim, we will analyze the metabolic phenotype of mice with adipose tissue-specific deletion of this adipokine gene. Our study will likely reveal the therapeutic potential of this adipokine in metabolic diseases.